1. Field of the Invention
This invention relates to a tangential flow filtration apparatus which includes a manifold system which effects small recirculation volumes.
2. Description of Prior Art
Tangential flow filtration (TFF) systems presently are commonly utilized to filter liquids to produce a permeate and a retentate. Liquid feed is directed tangentially across a porous membrane surface which is supported by a porous support such as a screen. The permeate and retentate then are recovered as separate streams.
TFF systems are commonly used to process biological liquids in order to concentrate biological molecules in a retentate for further study or use. It is not unusual that the biological molecules are present in the feed liquid in low concentrations. Thus, it is desirable to selectively separate a maximum volume of carrier liquid from the biological molecule of interest to maximize the concentration of the biological molecule in the retentate. This condition, in turn, facilitates further study or use of the biological molecule.
Presently available TFF apparatus are formed of a plurality of elements, including a pump, a feed solution reservoir, a filtration module and conduits for connecting these elements. In use, the feed solution is directed from the feed solution reservoir to the filtration module while the retentate from the filtration module is recirculated from the filtration module to the feed solution reservoir until the desired volume of retentate is obtained. The conduits each require an individual fitting. Assembly of the individual fittings to individual conduits is undesirably time consuming. In addition, when the total internal volume of the conduits used in the apparatus is increased, the recirculating volume of liquid is undesirably increased. It is desirable to minimize this recirculation volume in order to maximize the concentration of the product in the retentate. For example, the Ultralab system available from Pall-Filtron Corporation, East Hills, N.Y., has a minimum recirculation volume of 20-25ml when conduit lengths of the system are minimized. Also, the Amicon CH2 System available from Millipore Corporation, Bedford, Mass. has a minimum recirculation volume of 100 ml.
Accordingly, it would be desirable to provide a tangential flow filtration system which provides a reduced recirculation volume as compared to presently available tangential flow filtration systems. Such a system would permit maximizing the concentration of molecules of interest in a retentate stream thereby facilitating use or analysis of the molecules of interest. In addition, such a system would allow obtaining the same factors of the concentration of the molecules of interest with smaller starting volumes.
The present invention provides a tangential flow filtration apparatus which includes a reservoir for a fluid feed and a tangential flow filtration module which are connected together through manifolds. A pump is provided to direct fluid feed from the reservoir, through a manifold and into the filtration module where the fluid feed is separated to form a permeate and a retentate. The permeate is removed from the filtration module and recovered or discarded. The retentate is recycled to the reservoir through the second manifold so that it can be redirected into the filtration module. Pressure within a retentate conduit in fluid communication with the retentate exiting from the filtration module can be adjusted, such as with a valve to provide more uniform pressure drop through the membrane along the length of one or more filtration membranes positioned within the filtration module. The pump can be utilized as a unit separate from the reservoir and the filtration module or it can be formed integrally with the reservoir or with a support structure for the reservoir.
The tangential flow filtration apparatus of this invention eliminates the need for flexible tubular conduits from the filtration module to the liquid feed reservoir by utilizing a manifold formed integrally with the reservoir. This structure, in turn, permits providing a small minimum recirculation volume as compared to the filtration systems of the prior art which require the use of tubular conduits. In addition, the length of flexible tubular conduits can be minimized from the liquid feed reservoir to the filtration module by a second manifold formed integrally with the reservoir. Flexible tubular connections from the liquid feed reservoir to the filtration module can be eliminated when the pump is formed integrally with the reservoir or with a support for reservoir.